Microbiome-Gut-Brain Interactions in Neurodevelopmental Disorders: Focus on Autism and Schizophrenia

Human brain development is a complex process. For instance, in the third week of gestation, many of the %7E 86 billion neurons observed in the adult brain are being produced (1). Subsequently, there is a constant refining and fine-tuning of these connections that continues after birth until late adolescence. This process of circuit remodelling is critical for normal brain function and behaviour (2) and factors that interfere with these processes can result in brain miswiring and associated behavioural manifestations. Genetic and environmental factors have long been recognized to modulate this complex process of brain development (2). However, there is a growing appreciation of the role that bacterial commensals of the gastrointestinal (GI) system (collectively referred to as gut microbiota which also includes viruses, fungi and protozoans) have in shaping host health and behaviour following birth (3,4). The gut microbiota plays a critical role in the maturation of the immune system especially in the early stages of life. The colonization and development of gut microbiota in early life has been associated with disease later in life (5). The gut microbiota comprises trillions of bacteria, which play a key role in morphological and neurological processes such as brain development, neurotransmission, neuroinflammation, neurogenesis and modulation of behaviour (6-9). Deleterious alterations to the gut microbiota through various factors such as diet, age, stress, mode of delivery and antibiotic administration can disrupt brain physiology and behaviour. Administration of antibiotics is one such example, where ablation of the gut microbiota composition can result in cognitive impairments (10), metabolic alterations (11) and disrupted immune function (12). Cumulative data from both preclinical and clinical studies suggest a key role for the gut microbiota in the onset of various psychiatric and neurological conditions including depression (13,14), anxiety (15), stroke (16), autism (17) and schizophrenia (18).